title: IFN-γ production by CD27⁺ NK cells exacerbates Listeria monocytogenes infection in mice by inhibiting granulocyte mobilization.
abstract: Natural killer (NK) cells are key components of the immune system involved in several immune reactions, including the clearance of intracellular pathogens. When activated, NK cells rapidly secrete particular cytokines that activate innate immunity and facilitate development of adaptive responses. Conflicting reports on the role of NK cells during infection by Listeria monocytogenes can be found in the literature. Here, we demonstrate that during lethal infection by L. monocytogenes, activation of NK cells via the costimulatory molecule CD27 leads to excessive IFN-γ production. This impairs innate anti-bacterial host defenses by inducing downregulation of CXCR2 on granulocytes and consequently inhibiting their recruitment to the sites of infection. The use of antibodies to block CD27 signaling or to deplete IFN-γ was sufficient to rescue mice from lethal challenge by L. monocytogenes. Our findings contribute to a better understanding of the importance of CD27 signaling in activation of NK cells and should provide new ways of interfering with infections.
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, HZI, Braunschweig, Germany.
authors.forename: Nuno
authors.initials: N
authors.lastname: Viegas
authors.forename: Lisa
authors.initials: L
authors.lastname: Andzinski
authors.forename: Ching-Fang
authors.initials: CF
authors.lastname: Wu
authors.forename: Ronja-Melinda
authors.initials: RM
authors.lastname: Komoll
authors.forename: Nelson
authors.initials: N
authors.lastname: Gekara
authors.forename: Kurt E
authors.initials: KE
authors.lastname: Dittmar
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weiss
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Jablonska
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D006098:Granulocytes / Q000276:immunology* / Q000382:microbiology; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology / Q000378:metabolism*
chemical_list: D019138:Antibodies, Blocking; D023063:Receptors, Interleukin-8B; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007371:Interferon-gamma
keywords: Granulocytes; IFN-γ; Infection; Listeria monocytogenes; NK cells